Rheumatoid arthritis is a disease of unknown etiology. Considerable evidence indicates that the chronic articular and extra- articular inflammation in this disease results from immunological tissue injury. Recent observations indicate that antigen-antibody complexes exist in the synovial fluid and may well initiate the inflammation. However, the antigens involved have not been defined, but autologous gamma-globulin is a possibility. The definition of antigens involved can lead to elucidation of the mechanisms of this disease and even discovery of the cause of rheumatoid arthritis. During the proposed budget period our previous work on the self- association of IgG-rheumatoid factors will be extended to the study of synovial fluids obtained from patients with rheumatoid arthritis. Methods for detection of these complexes will be developed. Detailed studies will be carried out on selected synovial fluids.